Genetic analysis explores phenotypic differences in ALGS
No phenotypic differences were found in patients with Alagille syndrome (ALGS) with a truncating, non-truncating, or structural JAG1 variant, according to data from the largest comprehensive genetic analysis of individuals with ALGS presented at the 6th World Congress of Paediatric Gastroenterology, Hepatology and Nutrition.
In this international, multicenter retrospective study, 845 patients with ALGS, a pathogenic or likely pathogenic (LP) variant in JAG1 and NOTCH2 variant was found in 97.5% (n = 824) and 2.5% (n = 21), respectively. JAG1 variants were truncating in 73% (n = 604), non-truncating in 17% (n = 137), and structural variants in 10% (n = 83). In these patients with JAG1 variants, history of neonatal cholestasis (NC) was 82%, 81%, and 82%, respectively and presence of bile duct paucity was 66%, 55%, and 61%, respectively. No significant differences were found in the prevalence of extrahepatic manifestations.
In patients with prior NC and truncating (n = 473), non-truncating (n = 110), or structural JAG1 variant (n = 62), the 10- and 18-years TFS rate was comparable. At 10- and 18-years the OS rates were ≥88%.
History of NC, bile duct paucity, renal anomalies, and vascular anomalies were similar between patients with NOTCH2-and-JAG1. Patients with a NOTCH2 variant were significantly less likely than those with JAG1 variants to have characteristic facies, an ECHO confirmed cardiac anomaly, posterior embryotoxon, or butterfly vertebrae.
Vandriel SM, et al. Differential prevalence of extrahepatic clinical manifestations in patients with Jagged1 and NOTCH2-associated Alagille syndrome: Results from the International Multicenter GALA Study Group. Presented at: 6th World Congress of Paediatric Gastroenterology, Hepatology and Nutrition.